Effectiveness of Monovalent mRNA Vaccines Against COVID-19–Associated Hospitalization Among Immunocompetent Adults During BA.1/BA.2 and BA.4/BA.5 Predominant Periods of SARS-CoV-2 Omicron Variant in the United States — IVY Network, 18 States, December 26, 2021–August 31, 2022
Authors: Diya Surie, Levi Bonnell, Katherine Adams, Manjusha Gaglani, Adit A. Ginde, David J. Douin, H. Keipp Talbot, Jonathan D. Casey, Nicholas M. Mohr, Anne Zepeski, Tresa McNeal, Shekhar Ghamande, Kevin W. Gibbs, D. Clark Files, David N. Hager, Arber Shehu, Anne P. Frosch, Heidi L. Erickson, Michelle N. Gong, Amira Mohamed, Nicholas J. Johnson, Vasisht Srinivasan, Jay S. Steingrub, Ithan D. Peltan, Samuel M. Brown, Emily T. Martin, Akram Khan, William S. Bender, Abhijit Duggal, Jennifer G. Wilson, Nida Qadir, Steven Y. Chang, Christopher Mallow, Carolina Rivas, Jennie H. Kwon, Matthew C. Exline, Adam S. Lauring, Nathan I. Shapiro, Natasha Halasa, James D. Chappell, Carlos G. Grijalva, Todd W. Rice, William B. Stubblefield, Adrienne Baughman, Kelsey N. Womack, Kimberly W. Hart, Sydney A. Swan, Yuwei Zhu, Jennifer DeCuir, Mark W. Tenforde, Manish M. Patel, Meredith L. McMorrow, Wesley H. Self, Nicole Calhoun, Judy Herrick, Eric Hoffman, Amanda McKillop, Kempapura Murthy, Michael Smith, Martha Zayed, Lesley De Souza, Lori-Ann Kozikowski, Scott Ouellette, Kiran Ashok, Susan Gole, Alexander King, Omar Mehkri, Bryan Poynter, Caitlin ten Lohuis, Nicholas Stanley, Sean Caspers, Audrey Hendrickson, Olivia Kaus, Leyla Taghizadeh, Walker Tordsen, Valerie Aston, Robert Bowers, Jeffrey Jorgensen, Jennifer King, Harith Ali, Richard E. Rothman, Jen-Ting Chen, Rahul Nair, Gopal Allada, Genesis Briceno, Shewit Giovanni, Kinsley A. Hubel, Jesus Martinez, Minn Oh, Jonathan Pak, Jose Pena, Alexandra Jun Gordon, Joe Levitt, Cynthia Perez, Jonasel Roque, Anita Visweswaran, Sarah Karow, Maryiam Khan, Austin Klingler, Sarah Pannu, David Smith, Elizabeth Schwartz, Connor Snyder, Madison So, Preston So, Gabrielle Swoope, Michael Weigand, Michael Carricato, Ian Chambers, Conner Driver, Jennifer Goff, David Huynh, Kelly Jensen, Sukantha Chandrasekaran, Trevor Frankel, Omai Garner, Catherine Fairfield, Shannon Landers, Paul Nassar, Cameron Williams, Hayley Gershengorn, Ramsay Bielak, Christopher Blair, William J. Fitzsimmons, Rebecca Fong, Julie Gilbert, EJ McSpadden, Lara Thomas, Rachel Truscon, Weronika Damek Valvano, Layla A. Anderson, Christine D. Crider, Thomas C. Paulson, Kyle A. Steinbock, Marica Blair, Lauren J. Ezzell, Samarian J. Hargrave, Christy Kampe, Jakea Johnson, Jennifer L. Luther, Rendie E. McHenry, Bryan P. M. Peterson, Claudia Guevara Pulido, Laura L. Short, Margaret E. Whitsett, Madeline Hicks, Leigha Landreth, Mary LaRose, Lisa Parks, Hilary Babcock, Tiffany Hink, Kevin Jolani, David McDonald, Caroline O’Neal, Bijal Parikh, Katie Parrish, Carleigh Samuels
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

The SARS-CoV-2 Omicron variant (B.1.1.529 or BA.1) became predominant in the United States by late December 2021 (1). BA.1 has since been replaced by emerging lineages BA.2 (including BA.2.12.1) in March 2022, followed by BA.4 and BA.5, which have accounted for a majority of SARS-CoV-2 infections since late June 2022 (1). Data on the effectiveness of monovalent mRNA COVID-19 vaccines against BA.4/BA.5-associated hospitalizations are limited, and their interpretation is complicated by waning of vaccine-induced immunity (2-5). Further, infections with earlier Omicron lineages, including BA.1 and BA.2, reduce vaccine effectiveness (VE) estimates because certain persons in the referent unvaccinated group have protection from infection-induced immunity. The IVY Network† assessed effectiveness of 2, 3, and 4 doses of monovalent mRNA vaccines compared with no vaccination against COVID-19-associated hospitalization among immunocompetent adults aged ≥18 years during December 26, 2021-August 31, 2022. During the BA.1/BA.2 period, VE 14-150 days after a second dose was 63% and decreased to 34% after 150 days. Similarly, VE 7-120 days after a third dose was 79% and decreased to 41% after 120 days. VE 7-120 days after a fourth dose was 61%. During the BA.4/BA.5 period, similar trends were observed, although CIs for VE estimates between categories of time since the last dose overlapped. VE 14-150 days and >150 days after a second dose was 83% and 37%, respectively. VE 7-120 days and >120 days after a third dose was 60%and 29%, respectively. VE 7-120 days after the fourth dose was 61%. Protection against COVID-19-associated hospitalization waned even after a third dose. The newly authorized bivalent COVID-19 vaccines include mRNA from the ancestral SARS-CoV-2 strain and from shared mRNA components between BA.4 and BA.5 lineages and are expected to be more immunogenic against BA.4/BA.5 than monovalent mRNA COVID-19 vaccines (6-8). All eligible adults aged ≥18 years§ should receive a booster dose, which currently consists of a bivalent mRNA vaccine, to maximize protection against BA.4/BA.5 and prevent COVID-19-associated hospitalization.